Protective immunogenicity of the paraflagellar rod protein 2 of Leishmania mexicana.

Paraflagellar rod proteins (PFR) are a potent immunogen against experimental Trypanosoma cruzi infection. PFR are highly conserved among kinetoplastid parasites. We therefore evaluated the immunogenicity of the Leishmania mexicana pfr-2 gene and protein product in the hamster model of American cutaneous leishmaniasis. Immunization with pfr-2 DNA-induced specific antibody, confirming immunogenicity. Subsequent challenge with 10,000 and 500 stationary phase L. mexicana promastigotes respectively, resulted in delayed appearance of lesions, and significant reduction in lesions post infection in male hamsters, yet exacerbated lesions in female hamsters. Immunization with recombinant PFR-2 protein (rPFR-2) prevented lesion development in female hamsters challenged with L. panamensis, but was ineffective against L. mexicana. Nevertheless, prime boost immunization of female hamsters with rPFR and pfr-2 DNA significantly reduced lesion size following challenge with 500 L. mexicana promastigotes, supporting the relevance of PFR-2 as a potential vaccine constituent.

Evaluation of Etest for susceptibility testing of multidrug-resistant isolates of Mycobacterium tuberculosis.

To prescribe effective treatment schemes for patients with tuberculosis, more-efficient susceptibility testing techniques for Mycobacterium tuberculosis are needed, especially in regions with multidrug resistance. Etest (AB BIODISK, Solna, Sweden) is a simple technique that provides quantitative drug susceptibility results for M. tuberculosis in 5 to 10 days from a culture grown at low cost. The performance of Etest was compared to that of the reference proportion method, using 95 M. tuberculosis clinical isolates of which 42.1% (40 of 95) were resistant to at least one antibiotic by the reference method. Overall agreement between Etest and the reference method was 98.9% (94 of 95) for detection of multidrug resistance; for resistance to individual drugs, agreement was 97.9% (93 of 95) for rifampin, 96.0% (92 of 95) for ethambutol, 94.7% (90 of 95) for isoniazid, and 85.3% (81 of 95) for streptomycin. This study supports the utility of Etest for timely detection of drug resistance in M. tuberculosis and for use in tuberculosis control programs.

Clinical and programmatic mismanagement rather than community outbreak as the cause of chronic, drug-resistant tuberculosis in Buenaventura, Colombia, 1998.

SETTING: Buenaventura, Colombia. OBJECTIVE: To assess whether antituberculosis drug resistance was generated by poor management or community transmission. DESIGN: Treatment-failure and new tuberculosis (TB) patients identified between May 1997 and June 1998 were interviewed and their treatment histories reviewed. Bacteriologic testing, including drug susceptibility profiles (DSP) and DNA fingerprinting by restriction fragment length polymorphism (RFLP), was performed and human immunodeficiency virus (HIV) testing was offered. RESULTS: DSP and RFLP fingerprints were obtained for isolates from 34 of 64 treatment-failure patients; 25 (74%) were resistant to > or = one drug. Fifteen of the 25 patients consented to HIV testing; none were positive. An average of 2.8 major treatment errors per patient was identified. RFLP from the treatment-failure patients revealed 20 unique isolates and six clusters (isolates with identical RFLP); 4/6 clusters contained isolates with different DSP. Analysis of the RFLP from both treatment-failure and new patients revealed that 44/111 (40%) isolates formed 18 clusters. Four of 47 (9%) new patients had multidrug-resistant TB (MDR-TB). Eleven isolates belonged to the Beijing family, related to the MDR strain W. CONCLUSION: Drug resistance in Buenaventura results from both poor management and community transmission. Dependence on DSP to identify TB transmission is inadequate when programmatic mismanagement is common.